title: Predictors of pathological progression among men with localized prostate cancer undergoing active surveillance: a sub-analysis of the REDEEM study.
abstract: OBJECTIVE
  We identify risk factors for pathological progression among men on active surveillance in the REDEEM (REduction by Dutasteride of clinical progression Events in Expectant Management trial).
  
  
  METHODS
  REDEEM was a 3-year, randomized, double-blind study of patients in 65 North American academic centers. Eligible men were 48 to 82 years old, with low risk prostate cancer (T1c-T2a), Gleason score 6 or less, 3 or fewer cores positive, tumor less than 50% of any 1 core, serum prostate specific antigen 11 ng/ml or less, life expectancy greater than 5 years and undergoing active surveillance. Entry biopsies (10 cores or more) were required. The analysis included 276 patients with 1 biopsy or more after the start of study treatment. Patients received dutasteride 0.5 mg per day or placebo for 3 years. Time to pathological progression (volume [4 or more cores positive or 50% or greater of 1 core] or grade progression [Gleason score 7 or greater]) in a post-baseline biopsy (not preceded by therapeutic intervention), and baseline variables were analyzed using a Cox proportional hazard model.
  
  
  RESULTS
  In total 94 of 276 patients with a post-baseline biopsy (34.1%) had pathological progression, 54 (19.6%) had volume progression only, 19 (6.9%) had grade progression only and 21 (7.6%) had both types of progression. Older age (HR 1.05, 95% CI 1.01-1.08, p=0.009) and higher prostate specific antigen density (HR 1.06, 95% CI 1.04-1.09, p<0.001) were associated with pathological progression. Post-baseline prostate specific antigen identified grade, but not volume progression in patients treated with placebo and dutasteride.
  
  
  CONCLUSIONS
  Older age and higher prostate specific antigen density were independent predictors of pathological progression. Post-baseline measurements as predictors of pathological progression could not be established. Further studies are needed to evaluate the role of dutasteride and establish better markers of pathological progression in active surveillance.
authors.affiliation: (a)Division of Urology, Department of Surgical Oncology, Princess Margaret Hospital, University Health Network, Toronto, Ontario, Canada. Electronic address: sdmargel@gmail.com.
authors.forename: David
authors.initials: D
authors.lastname: Margel
authors.forename: Indrani
authors.initials: I
authors.lastname: Nandy
authors.forename: Timothy H
authors.initials: TH
authors.lastname: Wilson
authors.forename: Ramiro
authors.initials: R
authors.lastname: Castro
authors.forename: Neil
authors.initials: N
authors.lastname: Fleshner
mesh_terms: D058891:5-alpha Reductase Inhibitors / Q000627:therapeutic use; D000368:Aged; D000369:Aged, 80 and over; D001378:Azasteroids / Q000627:therapeutic use; D018450:Disease Progression; D004311:Double-Blind Method; D000068538:Dutasteride; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D011471:Prostatic Neoplasms / Q000473:pathology* / Q000517:prevention & control / Q000628:therapy*; D012307:Risk Factors; D057832:Watchful Waiting
chemical_list: D058891:5-alpha Reductase Inhibitors; D001378:Azasteroids; D000068538:Dutasteride
keywords: 5-ARI; 5α-reductase inhibitor; AS; DRE; I-PSS; International Prostate symptom Score; PSA; active surveillance; digital rectal examination; disease progression; dutasteride; prostate specific antigen; prostate-specific antigen; prostatic neoplasms; watchful waiting